PROJECT SUMMARY Background: There is great interest in the implementation of genomic medicine, i.e., using genomic information to inform patient care. As a result, patients with ?medically actionable? (preventable and/or treatable) genetic conditions are being identified, often as an unsolicited secondary finding or a result of screening in the absence of a clinically known condition. The identification of a previously unsuspected medically actionable condition enhances the ability of health care providers' (HCPs) to intervene early to prevent disease. However these results could place HCPs in the uncomfortable position of having to address important results that they are not expecting, prepared, or equipped to integrate into patients' medical care, which could lead to inappropriate decision-making and harm to patients. Significance: Understanding the impact of unsolicited genomic results on HCPs and the actions they take is crucial to the successful implementation of genomic medicine. Yet there is little knowledge of the benefits, concerns, and challenges HCPs perceive when faced with unsolicited genomic results and whether they find such information useful in patient care. Innovation: This study leverages the Electronic Medical Records and Genomics (eMERGE III) Network where positive results (pathogenic or likely pathogenic variants) in ~100 ?medically actionable genes? sequenced in 22,500 biobank participants across the 9 eMERGE sites will be returned to participants and their primary care and subspecialty HCPs, providing an unprecedented opportunity to assess the return of these (mostly unsolicited) results in a large and diverse population of HCPs in a real-world setting. Methodology: This is a mixed-methods study using surveys, interviews, and focus groups. Specific Aims: Aim 1 is to survey primary care +/- subspecialty HCPs within one month after they receive an unsolicited positive genomic sequencing result on a patient enrolled in eMERGE III to assess: 1a) HCPs' views regarding receiving these results including 1) their readiness based on their genetic knowledge, experience, and training, 2) the clinical utility, 3) the medical actionability, and 4) their care responsibilities versus those of other providers; and 1b) HCPs' behaviors including 1) discussions with patients, 2) actions taken/planned, and 3) perceived barriers to acting on the information. Aim 2 is to conduct in-depth qualitative interviews with subset of HCPs 6 months after receiving an unsolicited positive genomic result to assess 1) actions taken, and 2) the ELSI of receiving unsolicited results. For sites where negative reports are provided, we will assess HCPs' interpretation of negative results and actions taken. Aim 3 is to make recommendations for the return of unsolicited genomic results to HCPs and to conduct focus groups to vet the recommendations. Expected results: We expect to make recommendations that will maximize the ability of HCPs to integrate the findings into patient care and facilitate interactions with their patients in the return and follow-up of the results. These recommendations will inform implementation strategies for use of genomic results in healthcare.